The quest for vaccine-induced immune correlates of protection against tuberculosis
Elisa Nemes, Andrew Fioré-Gartland, César Boggiano, Margherita Coccia, Patricia D’Souza, Peter B. Gilbert, Ann M. Ginsberg, Ollivier Hyrien, Dominick J. Laddy, Karen W. Makar, M. Juliana McElrath, Lakshmi Ramachandra, Alexander C. Schmidt, Solmaz Shotorbani, Justine Sunshine, Georgia D. Tomaras, Wen‐Han Yu, Thomas J. Scriba, Nicole Frahm
Abstract
Immunization strategies against tuberculosis (TB) that confer better protection than neonatal vaccination with the 101-year-old Bacille Calmette-Guerin (BCG) are urgently needed to control the epidemic, but clinical development is hampered by a lack of established immune correlates of protection (CoPs). Two Phase 2b clinical trials offer the first opportunity to discover human CoPs against TB. Adolescent BCG re-vaccination showed partial protection against Mycobacterium tuberculosis(Mtb) infection, as measured by sustained IFNg release assay (IGRA) conversion. Adult M72/AS01E vaccination showed partial protection against pulmonary TB. We describe two collaborative research programs to discover CoPs against TB and ensure rigorous, streamlined use of available samples, involving international immunology experts in TB and state-of-the-art technologies, sponsors, and funders. Hypotheses covering immune responses thought to be important in protection against TB have been defined and prioritized. A statistical framework to integrate the data analysis strategy was developed. Exploratory analyses will be performed to generate novel hypotheses.